The long term objective of this program is to investigate pathways of intermediary metabolism, energy production, and energy utilization by the lung parenchyma. Substrate utilization including both transcellular uptake and intracellular metabolism will be studied. This work will provide a framework for the investigation of the interactions of toxic agents with the pulmonary parenchyma and the metabolic defense mechanisms employed by the lung to protect against cellular damage. During the current year, we will utilize the isolated, perfused rabbit lung model to study factors affecting the rate of p-nitroanisole oxidative demethylation. This reaction is a model substrate for a cytochrome P-450-linked mixed-function oxidation. The factors that will be evaluated are the relationship of mixed-function oxidation to the alveolar oxygen tension, a source of glucose, and energy requirements.